PRC1 sustains the integrity of neural fate in the absence of PRC2 function

eLife

Alireza Khodadadi-Jamayran¹  Milica Bulajić²  Esteban O Mazzoni²  Alexander Miller³  Ayana Sawai³  Sarah Pfennig³  Jeremy S Dasen³ 

[1]Applied Bioinformatics Laboratories, Office of Science and Research, NYU School of Medcine, New York, United States

[2]Department of Biology, New York University, New York, United States

[3]Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, United States

关键词: neural development;    motor neuron;    hox gene;    polycomb protein;    Chicken;    Mouse;   

DOI  :  10.7554/eLife.72769

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We found that PRC1 is essential for the specification of segmentally restricted spinal motor neuron (MN) subtypes, while PRC2 activity is dispensable to maintain MN positional identities during terminal differentiation. Mutation of the core PRC1 component Ring1 in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in Ring1 mutants is due to the suppression of Hox-dependent specification programs by derepressed Hox13 paralogs (Hoxa13, Hoxb13, Hoxc13, Hoxd13). These results indicate that PRC1 can function in the absence of de novo PRC2-dependent histone methylation to maintain chromatin topology and postmitotic neuronal fate.

【 授权许可】

CC BY